It is desirable to standardize the measurement of the potency of pharmaceutical compositions as there is an optimum potency and quality of active component that is effective in treating the disease for which it is administered.
Glatiramer acetate (GA, also known as Copolymer-1 (Physician's Desk Reference), Copolymer 1, Cop-1 or COPAXONE®), is an approved drug for the treatment of multiple sclerosis (MS). Glatiramer acetate consists of the acetate salts of synthetic polypeptides, containing four naturally occurring amino acids (Physician's Desk Reference): L-glutamic acid, L-alanine, L-tyrosine, and L-lysine (Physician's Desk Reference) with an average molar fraction of L-glutamic acid: 0.129-0.153; L-alanine: 0.392-0.462; L-tyrosine: 0.086-0.100; L-lysine: 0.300-0.374, respectively. The average molecular weight of glatiramer acetate is 4,700-11,000 daltons (Physician's Desk Reference). Chemically, glatiramer acetate is designated L-glutamic acid polymer with L-alanine, L-Lysine and L-tyrosine, acetate (salt) (Physician's Desk Reference). Its structural formula is:(Glu, Ala, Lys, Tyr)χ.χCH3COOH(C5H9NO4.C3H7NO2.C6H14N2O2.C9H11NO3)χ.χC2H4O2 CAS-147245-92-9
(Physician's Desk Reference). Glatiramer acetate is also written as: poly[L-Glu13-15, L-Ala39-46, L-Tyr8.6-10, L-Lys30-37]nCH3COOH.
Glatiramer acetate was shown to suppress experimental autoimmune encephalomyelitis (EAE)—an experimental model for multiple sclerosis (MS) in various animal species (Lando et al., 1979; Aharoni, 1993). Studies of murine EAE suggested that the protection against EAE is mediated by T cell activity (Aharoni, 1993). This protection from active induction of EAE by mouse spinal cord homogenate, in which several auto-antigens are involved, could be adoptively transferred to normal recipients by injection of glatiramer acetate-specific T suppressor cells (Aharoni, 1993). In phase III clinical trials, daily subcutaneous injections of glatiramer acetate were found to slow progression of disability and reduce the relapse rate in exacerbating-remitting multiple sclerosis (Johnson, 1987). Processes of manufacturing glatiramer acetate are described in U.S. Pat. Nos. 3,849,550 and 5,800,808 and PCT International Publication No. WO 00/05250.
It is commonly accepted that a high level of antigen specificity is a feature of T cell activation. The T cells of the immune system recognize immunogenic peptides complexed to the major histocompatibility complex (MHC) class II or I molecules, expressed on antigen presenting cells (APCs). The specificity of antigen recognition by T cells is defined by several parameters: 1) affinity of the T cell receptor to the MHC peptide complex; 2) primary sequence of the antigenic peptide; and 3) synergistic effects of certain amino acid combinations within the antigenic peptide. Based on current knowledge on the mechanism of action of glatiramer acetate, it is believed that the biological activity of glatiramer acetate in MS is mediated by immunomodulation of T cell activity.